Affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Korea.

ABSTRACT

Objectives: To evaluate the risk of fractures related with zolpidem in elderly insomnia patients.

Methods: Health claims data on the entire South Korean elderly population from January 2005 to June 2006 were extracted from the Health Insurance Review and Assessment Service database. We applied a case-crossover design. Cases were defined as insomnia patients who had a fracture diagnosis. We set the hazard period of 1 day length prior to the fracture date and four control periods of the same length at 5, 10, 15, and 20 weeks prior to the fracture date. Time independent confounding factors such as age, gender, lifestyle, cognitive function level, mobility, socioeconomic status, residential environment, and comorbidity could be controlled using the case-crossover design. Time dependent confounding factors, especially co-medication of patients during the study period, were adjusted by conditional logistic regression analysis. The odds ratios and their 95% confidence intervals (CIs) were estimated for the risk of fracture related to zolpidem.

Results: One thousand five hundred and eight cases of fracture were detected in insomnia patients during the study period. In our data, the use of zolpidem increased the risk of fracture significantly (adjusted odds ratio [aOR], 1.72; 95% CI, 1.37 to 2.16). However, the association between benzodiazepine hypnotics and the risk of fracture was not statistically significant (aOR, 1.00; 95% CI, 0.83 to 1.21). Likewise, the results were not statistically significant in stratified analysis with each benzodiazepine generic subgroup.

Conclusions: Zolpidem could increase the risk of fracture in elderly insomnia patients. Therefore zolpidem should be prescribed carefully and the elderly should be provided with sufficient patient education.

Mentions:
This study used a case-crossover design, and Figure 2 shows the schematization of the study. For each patient, one day right before the fracture occurred was established as the hazard period, and one day before each of 5 weeks, 10 weeks, 15 weeks, and 20 weeks from the hazard period is established as the control period, setting pairs as a ratio of 1:4 [29-31]. Fracture, by its nature, is not very likely to occur again once it occurs; thus we limited the control period to the period before the fracture occurred. It is known from existing research that a short-term harmful reaction such as a hangover usually does not occur for more than a day; thus we defined the length of the hazard period as one day before the fracture [11,19,32].

Mentions:
This study used a case-crossover design, and Figure 2 shows the schematization of the study. For each patient, one day right before the fracture occurred was established as the hazard period, and one day before each of 5 weeks, 10 weeks, 15 weeks, and 20 weeks from the hazard period is established as the control period, setting pairs as a ratio of 1:4 [29-31]. Fracture, by its nature, is not very likely to occur again once it occurs; thus we limited the control period to the period before the fracture occurred. It is known from existing research that a short-term harmful reaction such as a hangover usually does not occur for more than a day; thus we defined the length of the hazard period as one day before the fracture [11,19,32].

Bottom Line:
Time independent confounding factors such as age, gender, lifestyle, cognitive function level, mobility, socioeconomic status, residential environment, and comorbidity could be controlled using the case-crossover design.Time dependent confounding factors, especially co-medication of patients during the study period, were adjusted by conditional logistic regression analysis.Likewise, the results were not statistically significant in stratified analysis with each benzodiazepine generic subgroup.

Affiliation:
Department of Preventive Medicine, Seoul National University College of Medicine, Korea.

ABSTRACT

Objectives: To evaluate the risk of fractures related with zolpidem in elderly insomnia patients.

Methods: Health claims data on the entire South Korean elderly population from January 2005 to June 2006 were extracted from the Health Insurance Review and Assessment Service database. We applied a case-crossover design. Cases were defined as insomnia patients who had a fracture diagnosis. We set the hazard period of 1 day length prior to the fracture date and four control periods of the same length at 5, 10, 15, and 20 weeks prior to the fracture date. Time independent confounding factors such as age, gender, lifestyle, cognitive function level, mobility, socioeconomic status, residential environment, and comorbidity could be controlled using the case-crossover design. Time dependent confounding factors, especially co-medication of patients during the study period, were adjusted by conditional logistic regression analysis. The odds ratios and their 95% confidence intervals (CIs) were estimated for the risk of fracture related to zolpidem.

Results: One thousand five hundred and eight cases of fracture were detected in insomnia patients during the study period. In our data, the use of zolpidem increased the risk of fracture significantly (adjusted odds ratio [aOR], 1.72; 95% CI, 1.37 to 2.16). However, the association between benzodiazepine hypnotics and the risk of fracture was not statistically significant (aOR, 1.00; 95% CI, 0.83 to 1.21). Likewise, the results were not statistically significant in stratified analysis with each benzodiazepine generic subgroup.

Conclusions: Zolpidem could increase the risk of fracture in elderly insomnia patients. Therefore zolpidem should be prescribed carefully and the elderly should be provided with sufficient patient education.